crossing96/oncoscreening huggingface dataset:
Impact of renal function of patients with advanced urothelial cancer on eligibility for first-line chemotherapy and treatment outcomes.	OBJECTIVE: The aim of the study is to clarify the clinical effects of first-line chemotherapy regimens for advanced urothelial cancer on clinical responses and survival of patients grouped by renal function. METHODS: In this multicenter retrospective cohort study, 345 urothelial cancer patients received systemic chemotherapy for metastatic or unresectable disease in 17 centers (2004-10). RESULTS: Two hundred and forty-one patients were treated with methotrexate, vinblastine, doxorubicin and cisplatin/methotrexate, epirubicin and cisplatin (n = 136) or gemcitabine and cisplatin (n = 105) followed by carboplatin-based treatments, non-platinum treatments or other regimens. After 2008, gemcitabine and cisplatin was the most frequently used regimen in patients with an estimated glomerular filtration rate < 60 ml/min/1.73 m(2) and in those with estimated glomerular filtration rate ≥ 60 ml/min/1.73 m(2). The gemcitabine and cisplatin patients' complete response rate was 10.5% and their response rate was 52.4%, which was highest among all regimens. Gemcitabine and cisplatin demonstrated a better 3-year overall survival when the estimated glomerular filtration rate was ≥ 60 ml/min/1.73 m(2) (31.4%), but it tended to be worse when the estimated glomerular filtration rate was < 60 ml/min/1.73 m(2) (14.1%). In the latter cases, the dose reduction rate of gemcitabine and cisplatin was high (43.9%). Among the patients with estimated glomerular filtration rate < 60 ml/min/1.73 m(2), the 1-year overall survival of the patients treated with a reduced dose of gemcitabine and cisplatin was significantly lower than that of those treated with standard-dose gemcitabine and cisplatin (26.2 vs. 60.3%, respectively, P = 0.0108). CONCLUSIONS: Gemcitabine and cisplatin provided favorable responses and survival in patients with estimated glomerular filtration rate ≥ 60 ml/min/1.73 m(2) but unsatisfactory oncological outcomes in patients with estimated glomerular filtration rate < 60 ml/min/1.73 m(2), especially when treated with a reduced dose. Alternative regimens might be optimal rather than reduced-dose gemcitabine and cisplatin in patients with estimated glomerular filtration rate < 60 ml/min/1.73 m(2).	bladder
Implications of Definitive Prostate Cancer Therapy on Soft Tissue Margins and Survival in Patients Undergoing Radical Cystectomy for Bladder Urothelial Cancer.	PURPOSE: We evaluated the possibility of an existing link between definitive prostate cancer treatment and its effect on positive soft tissue surgical margins at radical cystectomy. A secondary objective was to determine whether definitive prostate cancer treatment was associated with bladder cancer survival end points. MATERIALS AND METHODS: There were 749 patients who underwent radical cystectomy between 2000 and 2013. After excluding females and patients with nonurothelial histologies 561 men were identified, of whom 69 (12.3%) received single or multimodal definitive prostate cancer treatment. Univariate and multivariable logistic regression was used to determine an association between clinical and pathological features such as definitive prostate cancer treatment and positive soft tissue surgical margins. Cox regression models and competing risk regression were used to investigate the impact of definitive prostate cancer treatment and positive surgical margins on survival. RESULTS: The median age of the male population was 70.0 years. There were 57 cases of positive soft tissue surgical margins in our cohort of 561 men (10.2%). Of men who underwent previous definitive prostate cancer treatment 20 of 69 (29.0%) had positive surgical margins compared to 37 of 492 (7.5%) who never received definitive prostate cancer treatment (p <0.0001). Brachytherapy, radiotherapy, hormonal therapy and radical prostatectomy significantly increased the rate of positive margins. Brachytherapy (OR 5.8), radiotherapy (OR 2.7) and hormonal therapy (OR 5.1) remained independent predictors of positive margins on multivariate analysis. Positive margins were associated with negative effects on recurrence-free (HR 3.1), cancer specific (HR 4.1) and overall survival (HR 2.8). CONCLUSIONS: Patients with a history of definitive prostate cancer treatment are at increased risk for positive soft tissue surgical margins. Positive margins significantly impact bladder cancer recurrence-free, cancer specific and overall survival following radical cystectomy. Careful patient counseling and surgical planning are crucial when treating patients undergoing radical cystectomy who have a history of definitive prostate cancer treatment.	bladder
Molecular markers in bladder cancer: Novel research frontiers.	Bladder cancer (BC) is a heterogeneous disease encompassing distinct biologic features that lead to extremely different clinical behaviors. In the last 20 years, great efforts have been made to predict disease outcome and response to treatment by developing risk assessment calculators based on multiple standard clinical-pathological factors, as well as by testing several molecular markers. Unfortunately, risk assessment calculators alone fail to accurately assess a single patient's prognosis and response to different treatment options. Several molecular markers easily assessable by routine immunohistochemical techniques hold promise for becoming widely available and cost-effective tools for a more reliable risk assessment, but none have yet entered routine clinical practice. Current research is therefore moving towards (i) identifying novel molecular markers; (ii) testing old and new markers in homogeneous patients' populations receiving homogeneous treatments; (iii) generating a multimarker panel that could be easily, and thus routinely, used in clinical practice; (iv) developing novel risk assessment tools, possibly combining standard clinical-pathological factors with molecular markers. This review analyses the emerging body of literature concerning novel biomarkers, ranging from genetic changes to altered expression of a huge variety of molecules, potentially involved in BC outcome and response to treatment. Findings suggest that some of these indicators, such as serum circulating tumor cells and tissue mitochondrial DNA, seem to be easily assessable and provide reliable information. Other markers, such as the phosphoinositide-3-kinase (PI3K)/AKT (serine-threonine kinase)/mTOR (mammalian target of rapamycin) pathway and epigenetic changes in DNA methylation seem to not only have prognostic/predictive value but also, most importantly, represent valuable therapeutic targets. Finally, there is increasing evidence that the development of novel risk assessment tools combining standard clinical-pathological factors with molecular markers represents a major quest in managing this poorly predictable disease.	bladder
Suburothelial and extrinsic lesions of the urinary bladder: radiologic and pathologic features with emphasis on MR imaging.	OBJECTIVE: The purpose of this article is to present a contemporary review of the imaging appearance of diseases which affect the deeper layers of the urinary bladder, including both suburothelial and extrinsic pathologies, using radiologic-pathologic correlation. CONCLUSION: Compared to the more common urothelial lesions, at cystoscopy, suburothelial and extrinsic diseases of the urinary bladder wall often have a non-specific appearance or may be occult. Cross-sectional imaging, in particular MRI, plays an integral role in diagnosis. Mesenchymal tumors have distinct imaging features on MRI. Leiomyomas are characteristically low signal intensity on T2-weighted (T2W) imaging and progressively enhance. Lipomas and lipomatous hypertrophy are diagnosed by the presence of macroscopic fat. Neurofibromas, hemangiomas, and paragangliomas are hyperintense on T2W sequences and hypervascular. Reactive lesions occur in the setting of chronic inflammation and include: nephrogenic adenoma, cystitis cystica, and cystitis glandularis. Imaging findings are commonly non-specific; however, a mass with internal cystic spaces in association with pelvic lipomatosis is suggestive of cystitis glandularis. Urachal anomalies may be complicated by infection or malignancy. Urachal mucinous adenocarcinoma has a poor prognosis and may present as a T2-hyperintense suburothelial/extrinsic mass centered in the bladder dome. Other diseases may extrinsically involve the urinary bladder by hematogenous and peritoneal spread, including infection, endometriosis, and malignancy. A familiarity with suburothelial and extrinsic pathologies of the urinary bladder is critical for the radiologist, who may be the first to suggest these diagnoses.	bladder
Mycotic Thoracic Aortic Aneurysm After Intravesical Bacillus Calmette-Guérin Treatment.	Bacillus Calmette-Guérin (BCG) is widely used for the treatment of bladder cancer. We report a case of BCG-associated mycotic thoracic aortic aneurysm that was successfully treated with resection and antimycobacterial therapy.	bladder
Prognostic Value of Beta-Tubulin-3 and c-Myc in Muscle Invasive Urothelial Carcinoma of the Bladder.	BACKGROUND: To date, putative prognostic biomarkers have shown limited utility from the clinical perspective for bladder urothelial carcinoma. Herein, the expression of beta-tubulin-3 and c-Myc was evaluated to determine their prognostic potential. METHODS: In formalin fixed-paraffin embedded blocks, immunohistochemical expression of c-Myc and beta-tubulin-3 was evaluated. H score ranging from 0 to 300 was obtained by multiplying the percentage of positive cells by intensity (0-3); c-Myc and beta-tubulin-3 expression was defined: 0: negative, 1: weakly positive, 2: strongly positive. RESULTS: beta-tubulin-3 and c-Myc immunoexpression was available for 46 cases. At the univariate analysis, node-involvement, beta-tubulin-3 and c-Myc overexpression discriminate shorter DFS (HR 2.19, p = 0.043; HR 3.10, p = 0.24 and HR 3.05, p = 0.011, respectively); 2-yrs DFS log-rank analysis according to low versus high level of immunoexpression were statistically significant; beta-tubulin-3, 53% low vs 12.7% high (p = value 0.02) and c-Myc 28 low vs 8 high (p-value 0.007). Patients displaying negative beta-tubulin-3/c-Myc had statistically significant better 2-yrs DFS than those with mixed expression or double positivity (54.5% versus 18.7% versus 0%, log-rank p = 0.006). CONCLUSIONS: c-Myc and beta-tubulin-3 show improvement for prognostic risk stratification in patients with muscle invasive bladder urothelial carcinoma. These molecular pathways may also be candidate to improve predictiveness to targeted therapies.	bladder
Bladder and gastric metastases from lung adenocarcinoma harboring codon 13 KRAS mutation: a case report with unusual clinical outcome.	AIMS AND BACKGROUND: Gastric and bladder metastases are rare in non-small-cell lung cancer (NSCLC) and the differential diagnosis with primary tumors requires an in-depth examination. KRAS gene mutations are the main oncogenic driver of lung adenocarcinoma in Caucasian patients, occurring in 25%-30% of cases, but their prognostic and predictive role is complex and not fully clarified. KRAS mutations in lung adenocarcinoma are considered negatively predictive for epidermal growth factor receptor tyrosine kinase inhibitors therapy as well as for adjuvant chemotherapy. In this report, the authors describe a case of lung adenocarcinoma harboring a codon 13 KRAS mutation detected in all the biopsies performed in unusual metastatic sites during an atypical disease course. CONCLUSIONS: Recently, a different prognostic significance of various KRAS mutations in lung adenocarcinoma has been suggested. Further studies on rare biomolecular alterations to identify subgroups of patients with different prognostic/predictive characteristics are needed.	bladder
Clinical Value of 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography in Upper Tract Urothelial Carcinoma: Impact on Detection of Metastases and Patient Management.	OBJECTIVE: To determine the diagnostic accuracy of 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) for detecting metastasis and its impact on patient management with upper tract urothelial carcinoma (UTUC). PATIENTS AND METHODS: Consecutive patients with UTUC underwent 18F-FDG PET/CT after CT for initial staging (n = 47) and for restaging at recurrence (n = 9). Diagnostic accuracy for detecting metastases with PET/CT and CT was compared statistically. The impact of PET/CT on patient management was assessed by comparing questionnaires that were completed by the attending physicians before and after PET/CT. RESULTS: In the lesion-based analysis, 142 lesions were diagnosed as metastases. The sensitivity of PET/CT was significantly better than that of CT (85 vs. 50%, p = 0.0001). In the patient-based analysis, 22 patients were diagnosed as having metastases. The sensitivity/specificity/accuracy of PET/CT tended to be superior to those of CT, but these values were not significantly different (95, 91, and 93% vs. 82, 85, and 84%; p = 0.25, 0.50, and 0.063, respectively). The clinicians changed their assessments of disease extent and management plans in 18 (32%) and 11 (20%) patients, respectively, based on the PET/CT results. CONCLUSIONS: The diagnostic accuracy of PET/CT for detecting metastasis was superior to that of CT. PET/CT provided additional information to the CT-based staging, which had an impact on patient management.	bladder
DNA methylation levels and long-term trihalomethane exposure in drinking water: an epigenome-wide association study.	Trihalomethanes (THM) are undesired disinfection byproducts (DBPs) formed during water treatment. Mice exposed to DBPs showed global DNA hypomethylation and c-myc and c-jun gene-specific hypomethylation, while evidence of epigenetic effects in humans is scarce. We explored the association between lifetime THM exposure and DNA methylation through an epigenome-wide association study. We selected 138 population-based controls from a case-control study of colorectal cancer conducted in Barcelona, Spain, exposed to average lifetime THM levels ≤85 μg/L vs. >85 μg/L (N = 68 and N = 70, respectively). Mean age of participants was 70 years, and 54% were male. Average lifetime THM level in the exposure groups was 64 and 130 µg/L, respectively. DNA was extracted from whole blood and was bisulphite converted to measure DNA methylation levels using the Illumina HumanMethylation450 BeadChip. Data preprocessing was performed using RnBeads. Methylation was compared between exposure groups using empirical Bayes moderated linear regression for CpG sites and Gaussian kernel for CpG regions. ConsensusPathDB was used for gene set enrichment. Statistically significant differences in methylation between exposure groups was found in 140 CpG sites and 30 gene-related regions, after false discovery rate <0.05 and adjustment for age, sex, methylation first principal component, and blood cell proportion. The annotated genes were localized to several cancer pathways. Among them, 29 CpGs had methylation levels associated with THM levels (|Δβ|≥0.05) located in 11 genes associated with cancer in other studies. Our results suggest that THM exposure may affect DNA methylation in genes related to tumors, including colorectal and bladder cancers. Future confirmation studies are required.	bladder
Intravesical administration of exogenous microRNA-145 as a therapy for mouse orthotopic human bladder cancer xenograft.	We previously reported that the level of microRNA (miR)-145 is attenuated in human bladder cancer cells. In this current study, we investigated whether intravesical administration of miR-145 could be a potential therapeutic strategy for controlling bladder cancer by using an orthotopic human bladder cancer xenograft model. Following transfection of 253J B-V cells with miR-145, the effects of the ectopic expression of miR-145 were examined by performing MTT, Western blotting analysis, Hoechst33342 staining, and wound healing assay in vitro. Also, a mouse orthotopic human bladder cancer model was established by inoculating 253J B-V cells into the bladder wall of mice. The anti-cancer effects of intravesical injections of miR-145 into these mice were then assessed. Transfection of 253J B-V cells with miR-145 induced apoptosis and suppression of cell migration in vitro. Western blotting showed that the levels of c-Myc, socs7, FSCN1, E-cadherin, β-catenin, and catenin δ-1 were decreased and that the PI3K/Akt and Erk1/2 signaling pathways were increased in compensatory fashion. In vivo, mice treated with miR-145 showed 76% inhibition of tumor growth, with a significant prolongation of animal survival (p = 0.0183 vs. control). Western blotting showed that both apoptosis and cell motility-related genes were significantly decreased as seen in vitro. Furthermore, PI3k/Akt and Erk1/2 signaling pathways, which were activated in a compensatory manner in vitro, were decreased in vivo. Intravesical administration of exogenous miR-145 was thus concluded to be a valid therapy for bladder cancer in this human bladder cancer xenograft model.	bladder
Preoperative lymphocyte-monocyte and platelet-lymphocyte ratios as predictors of overall survival in patients with bladder cancer undergoing radical cystectomy.	Although pretreatment neutrophil-lymphocyte ratio (NLR), lymphocyte-monocyte ratio (LMR), and platelet-lymphocyte ratio (PLR) are reportedly associated with clinical outcomes of many cancers, their roles in patients with bladder cancer (BCa) who undergo radical cystectomy (RC) have not been widely investigated. We analyzed relationships between preoperative NLR, LMR, PLR, and overall survival (OS) in 124 BCa patients undergoing RC. OS curves were drawn using the Kaplan-Meier method and evaluated using the log-rank test. Relationships between OS and potential confounding variables were determined using Cox's proportional hazard regression model. Decreased LMR was associated with shorter OS (P = 0.012); OS in the low PLR group was significantly longer than that in the high PLR group (P = 0.029), and NLR was not significantly associated with oncological outcomes. However, after adjusting for confounding variables, patients in the high-LMR group indicated >30% decreased mortality than the low-LMR group (hazard ratio 0.674; 95% confidence interval 0.412-0.890; P = 0.003), and PLR was not an independent predictor of OS. Our results show that preoperative LMR is a better prognostic factor in BCa patients undergoing RC, compared with NLR and PLR.	bladder
Urologic and male genital manifestations of granulomatosis with polyangiitis.	Granulomatosis with polyangiitis (GPA) is a systemic necrotizing granulomatous vasculitis, which predominantly affects small-sized blood vessels. Major organ involvement includes the upper/lower respiratory tract and kidneys. In contrast, genitourinary disease is rare in GPA patients, reported in <1% of cases in large cohorts. Manifestations at this level include prostatitis, destructive urethritis, genital ulcers, orchitis and renal masses. Also, high-dose cyclophosphamide, one of the main immunosuppressive drugs used for GPA treatment, is associated with bladder toxicity, i.e., hemorrhagic cystitis and cancer. Here, we review the main urogenital symptoms associated with this ANCA-associated vasculitis. In addition, cyclophosphamide-induced urologic complications are detailed.	bladder
Sensitivity of initial biopsy or transurethral resection of bladder tumor(s) for detecting histological variants on radical cystectomy.	BACKGROUND: To investigate the efficacy of initial biopsy or transurethral resection of bladder tumor for detecting histological variants on radical cystectomy and to assess the prognostic significance of variant histology on urothelial carcinoma outcomes after radical cystectomy. METHODS: Clinical and histopathological characteristics of 147 patients with variant histology who underwent radical cystectomy for urothelial carcinoma between 2006 and 2012 were assessed. Sensitivity was calculated as the proportion of radical cystectomy specimens with a particular variant that also presented the variant in the biopsy or transurethral resection specimen. The Kaplan-Meier method and multivariate Cox proportional hazard regression analysis were used to estimate cancer-specific survival. RESULTS: Of the 147 patients, 116 (79 %) were diagnosed with a single variant histology, and 31 (21 %) had multiple patterns. Squamous differentiation (31 %) was the most common single variant histology, followed by glandular differentiation (28 %). Except for small cell variant (100 %), the sensitivity of biopsy and transurethral resection was most effective for the diagnosis of squamous differentiation, 19 % vs. 40 % respectively, followed by glandular differentiation, 11 % vs. 21 % respectively. A total of 6 % and 49 % patients could be variant-free partially due to biopsy or complete resection(s) respectively. Presence of variant differentiation in urothelial carcinoma at cystectomy was significantly associated with inferior survival both in univariate analysis (P = 0.005) and multivariate analysis (HR4.48, 95 % CI:1.03-19.53). CONCLUSIONS: Overall sensitivity of biopsy or transurethral resection to detect variant differentiation on cystectomy is relatively low. Patients with variant differentiation on cystectomy specimens have inferior survival.	bladder
Molecular events are associated with resistance to vinblastine in bladder cancer.	Bladder cancer occurs in the majority of cases in males, which represents the fourth highest incident cancer in men and tenth in women. It is associated with a high rate of recurrence, and prognosis is poor once the cancer metastasizes to distant sites. Transitional cell cancer (TCC) is the most predominant histological type. Bladder cancer is highly chemosensitive. However, the presence of acquired drug resistance is one of the primary impediments to the success of chemotherapy. To differentiate and delineate the molecular events, we developed drug resistant human transitional bladder cancer T24 cells (DRC) by treating cells with the increasing concentration of vinblastine. We found that DRC was resistant to vinblastine in comparison to parental T24 cells. We analyzed the contributory factors that may be involved in the development of resistance. As expected, expression of permeability glycoprotein (P&mdash;gp) was up&mdash;regulated in DRC. In addition, levels of Caveolin&mdash;1 (Cav&mdash;1), Fatty acid synthase (FASN) and Cytochrome P450 (CYP450) were elevated in DRC. Downregulation of these proteins by respective specific pharmacological inhibitors and/or by siRNAs resensitized cells to vinblastine. These results suggested that differential levels of P&mdash;gp, Cav&mdash;1 and FASN except CYP450 play a major role in acquired resistant phenotype in bladder cancer.	bladder